Rheumatoid arthritis (RA) is a chronic systemic disorder of unknown etiology. Previously our laboratory has shown that the destruction of joints is mediated by proliferating transformed-appearing synovial lining cells expressing ras and myc oncogenes. Based on this observation, we searched for evidence of transforming factors especially retroviral antigens in the RA synovium. Immunohistology and electron microscopy revealed spherical particles with a diameter of 200 nm and a core of 70 nm, lacking epitopes for HTLV-I p19 and HIV-I p24. Although these particles bear a striking resemblance to type C retroviral particles, they do not resemble any of known human retroviruses, including particles from known endogenous retroviraI structures. Consequently, in this project we propose to use primers from highly conserved pol regions to identify the virus-like particles by polymerase chain reaction (PCR). We will produce polspecific DNA fragments from purified viral-particle RNA and determine the sequence of the amplified fragments following molecular cloning. These studies are aimed to design novel strategies to test the hypothesis that a hitherto unknown retrovirus could account for the two dominant processes - T cell dependent immune responses and synovial hyperplasia - operating In the pathogenesis of RA.